grpE Resolved · high auto-curated
H37Rv Rv0351 · MTBC0 mtbc0_000372 ·
235 aa · 425032–425739 (+) ·
RefSeq NP_214865.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | stress response protein GrpE |
|---|---|
| MTBC0 PGAP re-annotation | nucleotide exchange factor GrpE |
| Revised (this work) | Nucleotide exchange factor GrpE. Pfam: GrpE (PF01025.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMT5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Protein GrpE |
| Curated function | Participates actively in the response to hyperosmotic and heat shock by preventing the aggregation of stress-denatured proteins, in association with DnaK and GrpE. It is the nucleotide exchange factor for DnaK and may function as a thermosensor. Unfolded proteins bind initially to DnaJ; upon interaction with the DnaJ-bound protein, DnaK hydrolyzes its bound ATP, resulting in the formation of a stable complex. GrpE releases ADP from DnaK; ATP binding to DnaK triggers the release of the substrate protein, thus completing the reaction cycle. Several rounds of ATP-dependent interactions between Dn. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | grpE |
| eggNOG description | Participates actively in the response to hyperosmotic and heat shock by preventing the aggregation of stress-denatured proteins, in association with DnaK and GrpE. It is the nucleotide exchange factor for DnaK and may function as a thermosensor. Unfolded proteins bind initially to DnaJ |
| Orthologous group | COG0576 |
| KEGG orthology |
K03687
|
| Gene Ontology (41) |
GO:0000166, GO:0000774, GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005623, GO:0006950, GO:0007154, GO:0008150, GO:0009267 +29 more
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.672 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
GrpE | PF01025.25 | 7.4e-28 | 49–187 | GrpE |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dnaK (chaperone protein DnaK), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0350 dnaK |
chaperone protein DnaK | 999 | 999 ctx | neighborhood:882 coexpression:964 experimental:773 textmining:939 |
Rv0352 dnaJ1 |
chaperone protein DnaJ | 999 | 999 ctx | neighborhood:829 coexpression:984 experimental:439 textmining:948 |
Rv0353 hspR |
heat shock protein transcriptional repressor HspR | 995 | 975 ctx | neighborhood:829 coexpression:857 textmining:829 |
Rv0384c clpB |
chaperone protein ClpB | 996 | 957 | coexpression:948 textmining:933 |
Rv0440 groEL2 |
molecular chaperone GroEL | 991 | 948 | coexpression:834 experimental:437 database:455 textmining:851 |
Rv3446c hyp |
hypothetical protein | 961 | 947 | coexpression:702 experimental:773 |
Rv0312 hyp |
hypothetical protein | 961 | 947 | coexpression:704 experimental:773 |
Rv2264c hyp |
hypothetical protein | 961 | 947 | coexpression:703 experimental:773 |
Rv3417c groEL1 |
chaperonin GroEL | 981 | 929 | coexpression:747 experimental:437 database:455 textmining:753 |
Rv3418c groES |
chaperonin GroES | 984 | 913 | coexpression:893 textmining:828 |
Rv2373c dnaJ2 |
chaperone protein DnaJ | 969 | 902 | coexpression:748 experimental:439 textmining:707 |
Rv2374c hrcA |
heat-inducible transcription repressor HrcA | 963 | 869 | coexpression:858 textmining:735 |
Rv3596c clpC1 |
ATP-dependent protease ATP-binding subunit ClpC | 908 | 768 | coexpression:718 textmining:620 |
Rv2667 clpC2 |
ATP-dependent protease ATP-binding subunit ClpC | 830 | 761 | coexpression:709 |
Rv2299c htpG |
chaperone protein HtpG | 821 | 756 | coexpression:718 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: stress response protein GrpE
- MTBC0 PGAP product: nucleotide exchange factor GrpE
- Pfam (hmmscan --cut_ga): GrpE PF01025.25 (E=7e-28)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_214865.1)
- Domains: Pfam-A via hmmscan --cut_ga — GrpE (PF01025.25)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0576 - Curated reference: UniProt P9WMT5 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
113 functional partner(s); context anchor
dnaK - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000372|Rv0351|grpE MTDGNQKPDGNSGEQVTVTDKRRIDPETGEVRHVPPGDMPGGTAAADAAHTEDKVAELTADLQRVQADFANYRKRALRDQQAAADRAKASVVSQLLGVLDDLERARKHGDLESGPLKSVADKLDSALTGLGLVAFGAEGEDFDPVLHEAVQHEGDGGQGSKPVIGTVMRQGYQLGEQVLRHALVGVVDTVVVDAAELESVDDGTAVADTAENDQADQGNSADTSGEQAESEPSGS